The purpose of this project is three fold: (1) to assess the specificity of a tris-sulfotyrosyl dodecapeptide (3S-peptide-I) at preventing dephosphorylation of the insulin receptor in a semi-permeabilized cell model; (2) to measure the extent of ligand-stimulated insulin receptor phosphorylation and signalling in intact cells incubated in the presence of the peptide; and (3) Compare these effects of 3S-peptide-I with those obtained in cells expressing the EGF receptors. Chinese hamster ovary cells transfected with the human insulin receptors (CHO/HIRc) or the EGF receptors (CHO/EGF-R) were used to test the specificity of 3S-peptide-I. We have found that 3S-peptide-I selectively enhances insulin receptor function in intact cells possibly as a result of inhibition of endogenous PTPases acting on the insulin receptor.